Up-regulation of intracellular signalling pathways may play a central pathogenic role in hypertension, atherogenesis, insulin resistance, and cancer promotion--the 'PKC syndrome'

"Abstract

The modern diet is greatly different from that of our paleolithic forebears' in a number of respects. There is reason to believe that many of these dietary shifts can up-regulate intracellular signalling pathways mediated by free intracellular calcium and protein kinase C, particularly in vascular smooth muscle cells; this disorder of intracellular regulation is given the name 'PKC syndrome'. PKC syndrome may entail either a constitutive activation of these pathways, or a sensitization to activation by various agonists. The modern dietary perturbations which tend to induce PKC syndrome may include increased dietary fat and sodium, and decreased intakes of omega-3 fats, potassium, calcium, magnesium and chromium. Insulin resistancemay be both a cause and effect of PKC syndrome, and weight reduction and aerobic training should act to combat this disorder. PKC syndrome sensitizes vascular smooth muscle cells to both vasoconstrictors and growth factors, and thus promotes both hypertension and atherogenesis. In platelets, it induces hyperaggregability, while in the microvasculature it may be a mediator of diabetic microangiopathy. In vascular endothelium, intimal macrophages, and hepatocytes, increased protein kinase C activity can be expected to increase cardiovascular risk. Up-regulation of protein kinase C in stem cells may also play a role in the promotion of 'Western' fat-related cancers. Practical guidelines for combatting PKC syndrome are suggested."

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The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic

"Abstract

OBJECTIVE:

Field studies of twentieth century hunter-gathers (HG) showed them to be generally free of the signs and symptoms of cardiovascular disease (CVD). Consequently, the characterization of HG diets may have important implications in designing therapeutic diets that reduce the risk for CVD in Westernized societies. Based upon limited ethnographic data (n=58 HG societies) and a single quantitative dietary study, it has been commonly inferred that gathered plant foods provided the dominant energy source in HG diets.

METHOD AND RESULTS:

In this review we have analyzed the 13 known quantitative dietary studies of HG and demonstrate that animal food actually provided the dominant (65%) energy source, while gathered plant foods comprised the remainder (35%). This data is consistent with a more recent, comprehensive review of the entire ethnographic data (n=229 HG societies) that showed the mean subsistence dependence upon gathered plant foods was 32%, whereas it was 68% for animal foods. Other evidence, including isotopic analyses of Paleolithic hominid collagen tissue, reductions in hominid gut size, low activity levels of certain enzymes, and optimal foraging data all point toward a long history of meat-based diets in our species. Because increasing meat consumption in Western diets is frequently associated with increased risk for CVD mortality, it is seemingly paradoxicalthat HG societies, who consume the majority of their energy from animal food, have been shown to be relatively free of the signs and symptoms of CVD.

CONCLUSION:

The high reliance upon animal-based foods would not have necessarily elicited unfavorable blood lipid profiles because of the hypolipidemic effects of high dietary protein (19-35% energy) and the relatively low level of dietary carbohydrate (22-40% energy). Although fat intake (28-58% energy) would have been similar to or higher than that found in Western diets, it is likely that important qualitative differences in fat intake, including relatively high levels of MUFA and PUFA and a lower omega-6/omega-3 fatty acid ratio, would have served to inhibit the development of CVD. Other dietary characteristics including high intakes of antioxidants, fiber, vitamins and phytochemicals along with a low salt intake may have operated synergistically with lifestyle characteristics (more exercise, less stress and no smoking) to further deter the development of CVD."

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A Paleolithic diet confers higher insulin sensitivity, lower C-reactive protein and lower blood pressure than a cereal-based diet in domestic pigs

"Abstract

BACKGROUND:

A Paleolithic diet has been suggested to be more in concordance with human evolutionary legacy than a cereal based diet. This might explain the lower incidence among hunter-gatherers of diseases of affluence such as type 2 diabetes, obesity and cardiovascular disease. The aim of this study was to experimentally study the long-term effect of a Paleolithic diet on risk factors for these diseases in domestic pigs. We examined glucose tolerance, post-challenge insulin response, plasma C-reactive protein and blood pressure after 15 months on Paleolithic diet in comparison with a cereal based swine feed.

METHODS:

Upon weaning twenty-four piglets were randomly allocated either to cereal based swine feed (Cereal group) or cereal free Paleolithic dietconsisting of vegetables, fruit, meat and a small amount of tubers (Paleolithic group). At 17 months of age an intravenous glucose tolerance test was performed and pancreas specimens were collected for immunohistochemistry. Group comparisons of continuous variables were made by use of the t-test. P < 0.05 was chosen for statistical significance. Simple and multivariate correlations were evaluated by use of linear regression analysis.

RESULTS:

At the end of the study the Paleolithic group weighed 22% less and had 43% lower subcutaneous fat thickness at mid sternum. No significant difference was seen in fasting glucose between groups. Dynamic insulin sensitivity was significantly higher (p = 0.004) and the insulinresponse was significantly lower in the Paleolithic group (p = 0.001). The geometric mean of C-reactive protein was 82% lower (p = 0.0007) and intra-arterial diastolic blood pressure was 13% lower in the Paleolithic group (p = 0.007). In evaluations of multivariate correlations, diet emerged as the strongest explanatory variable for the variations in dynamic insulin sensitivity, insulin response, C-reactive protein and diastolic blood pressure when compared to other relevant variables such as weight and subcutaneous fat thickness at mid sternum. There was no obvious immunohistochemical difference in pancreatic islets between the groups, but leukocytes were clearly more frequent in sampled pancreas from the Cereal group.

CONCLUSION:

This study in domestic pigs suggests that a Paleolithic diet conferred higher insulin sensitivity, lower C-reactive protein and lowerblood pressure when compared to a cereal based diet."

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Effects of a short-term intervention with a paleolithic diet in healthy volunteers

"Abstract

OBJECTIVES:

Prevention of cardiovascular diseases by paleolithic or hunter-gatherer diets has been discussed during recent years.

METHODS:

Our aim was to assess the effect of a paleolithic diet in a pilot study on healthy volunteers during 3 weeks. The intention was to include 20 subjects, of whom 14 fulfilled the study. Complete dietary assessment was available for six subjects.

RESULTS:

Mean weight decreased by 2.3 kg (P<0.001), body mass index by 0.8 (P<0.001), waist circumference by 0.5 cm (P=0.001), systolic blood pressure by 3 mm Hg (P=0.03) and plasminogen activator inhibitor-1 by 72% (P=0.020). Regarding nutrient intake, intake of energy decreased by 36%, and other effects were also observed, both favourable (fat composition, antioxidants, potassium-sodium rate) and unfavourable (calcium).

CONCLUSION:

This short-term intervention showed some favourable effects by the diet, but further studies, including control group, are needed."

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